Roles for integrin α3β1 in regulating the ability of epithelial cells to modulate the microenvironment during normal and pathological tissue remodeling

Am J Physiol Cell Physiol. 2024 Mar 18. doi: 10.1152/ajpcell.00128.2024. Online ahead of print.ABSTRACTIntegrin receptors for the extracellular matrix activate intracellular signaling pathways that are critical for tissue development, homeostasis, and regeneration/repair, and their loss or dysregulation contributes to many developmental defects and tissue pathologies. This review will focus on tissue remodeling roles for integrin α3β1, a receptor for laminins found in the basement membranes that underlie epithelial cell layers. As a paradigm, we will discuss literature that supports a role for α3β1 in promoting ability of epidermal keratinocytes to modify their tissue microenvironment during skin development, wound healing or tumorigenesis. Preclinical and clinical studies have shown that this role depends largely on ability of α3β1 to govern the keratinocyte's repertoire of secreted proteins, or the "secretome", including (1) matrix proteins and proteases involved in matrix remodeling and (2) paracrine-acting growth factors/cytokines that stimulate other cells with important tissue remodeling functions (e.g., endothelial cells, fibroblasts, inflammatory cells). Moreover, α3β1 signaling controls gene expression that helps epithelial cells carry out these functions, including genes that encode secreted matrix proteins, proteases, growth factors, or cytokines. We will review what is known about α3β1-dependent gene regulation through both transcription and post-transcr...
Source: Am J Physiol Cell Ph... - Category: Cytology Authors: Source Type: research